POS0531 ABATACEPT DELAYS THE DEVELOPMENT OF RA– CLINICAL RESULTS AFTER 18 MONTHS FROM THE RANDOMIZED, PLACEBO-CONTROLLED ARIAA STUDY IN RA-AT RISK PATIENTS
Authors: J. Rech, A. Kleyer, M. Østergaard, M. Hagen, L. Valor, K. Tascilar, G. Krönke, V. Schönau, S. Kleinert, X. Baraliakos, J. Braun, M. Fleck, A. Rubbert-Roth, F. Behrens, M. Feuchtenberger, M. Zaenker, D. M. Kofler, R. Voll, C. Glaser, A. Hueber, E. Feist, G. R. Burmester, K. Karberg, J. Strunk, J. D. D. Cañete, L. Šenolt, E. Naredo, G. Schett
Journal: Annals of the Rheumatic Diseases (2022)

Background The development of RA is described by a preclinical phase of autoimmunity, that precedes clinical disease. This autoimmune phase is characterized by the presence of anti-modified protein antibodies that recognize citrullinated proteins (ACPA). A subset of individuals with ACPA develops RA, i.e. those with imaging signs of subclinical inflammation in the joints. As T cell mediated B cell activation is a key step in developing autoimmunity and RA, interventions that target this process may be useful for preventing the onset of RA. In this context, abatacept seems being an attractive therapeutic tool as it interrupts the activation of T cells and has a favourable safety profile in the treatment of RA. Objectives To test whether treatment of abatacept, as compared to placebo, delays the onset of RA in ACPA positive individuals with a high risk to develop RA. Methods ARIAA is an international, randomized double-blinded placebo-controlled multi-center study in RA-at risk individuals, being ACPA positive and showing MRI signs of inflammation. The study was composed of a 6 months treatment phase with either abatacept s.c. 125 mg weekly or placebo and a 12 months observation phase with no treatment. Primary endpoint was the improvement of MRI inflammation after 6 months, secondary endpoints were the progression to RA after 6 and 18 months. The primary analysis was done on the ITT population and missing values were classified as treatment failures. Results Between November 2014 and December 2019 139 RA-at risk individuals were included into ARIAA by 14 study sites (11 in Germany, 1 in the Czech Republic and 2 in Spain). Of them, 100 patients were randomized to receive either abatacept or placebo. Two patients were excluded and 98 patients could be evaluated for efficacy and safety. The primary endpoint was met: 61% of abatacept and 31% of placebo treated individuals (p=0.0043) improved in MRI inflammation. Furthermore, only 4 patients (8.2%) in the abatacept group but 17 patients in the placebo group (34.7%) progressed to RA after 6 months (p= 0.0025). Even 1 year after cessation of treatment (18 months after inclusion) the number of patients progressing to RA was lower in the abatacept group (35%) than in the placebo group (57%; p=0.0421). With respect to safety, 12 serious adverse events (each one gastritis, cellulitis, pneumonia, tendinitis calcificans, rotator cuff syndrome, cholelithiasis, peripheral artery disease, idiopathic pain syndrome, prostate cancer, penile neoplasm; trabeculectomy, cataract surgery) were reported, with only one (pneumonia) being considered to be related to treatment. Conclusion Abatacept significantly reduces subclinical joint inflammation and delays the development of RA in at-risk individuals. Table 1. ABA PBO All N 49 49 98 Females, N (%) 31 (63.3) 39 (79.6) 70 (71.4) Age (ys); mean (±SD) 51.3 (±10.8) 48.5 (±12.6) 49.9 (±11.7) SJC (N); mean (±SD) 0 0 0 TJC (N); mean (±SD) 3.06 (± 3.75) 3.51 (± 4.42) 3.29 (±4.08) VAS Pain (mm) mean (±SD) 42.2 (± 27.1) 42.8 (± 33.2) 42.5 (± 30.2) VAS PG (mm) mean (±SD 42.2 (±28.7) 43.0 (± 33.8) 42.6 (± 31.2) MRI improvement, N (%) 30 (61.2) 15 (30.6) 45 (45.9) RA at 6 months, N (%) 4 (8.2) 17 (34.7) 21 (21.4) RA at 18 months, N (%) 17 (34.7) 28 (57.1) 45 (45.9) Acknowledgements The study was supported by BMS according to the items outlined in the IIS contract and the IMI funded project RTCure. Disclosure of Interests Jürgen Rech Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultancy: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Sobi, Novartis, Arnd Kleyer Consultant of: BMS, Pfizer, Sanofi, Abbvie, Janssen, Medac, Novartis, Lilly Deutschland GmbH, Gilead, Amgen, Grant/research support from: Novartis, Lilly Deutschland GmbH, Mikkel Østergaard: None declared, Melanie Hagen: None declared, Larissa Valor: None declared, Koray Tascilar: None declared, Gerhard Krönke: None declared, Verena Schönau: None declared, Stefan Kleinert: None declared, Xenofon Baraliakos: None declared, Juergen Braun: None declared, Martin Fleck: None declared, Andrea Rubbert-Roth: None declared, Frank Behrens: None declared, Martin Feuchtenberger: None declared, Michael Zaenker: None declared, David M Kofler: None declared, Reinhard Voll: None declared, Cornelia Glaser: None declared, Axel Hueber: None declared, Eugen Feist: None declared, Gerd Rüdiger Burmester: None declared, Kirsten Karberg: None declared, Johannes Strunk: None declared, Juan de Dios Cañete: None declared, Ladislav Šenolt: None declared, Esperanza Naredo: None declared, Georg Schett: None declared.